The Integration of Feedforward Locomotor Commands and Sensory Feedback Signals by Medullary Reticulospinal Neurons that Mediate Postural Responses

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 DESCRIPTION (provided by applicant): Fall-related injuries represent a significant public health problem. While the etiology of falling is complex and varies considerably from person to person, it is widely recognized that individuals with poor postural control, a major contributor to fall risk, frequently have deficits in sensory function. The maintenance of stable posture is an inherently multisensory process requiring the integration of visual, vestibular, and somatic inputs from the limb. The importance of the proprioceptive senses is highlighted following its loss, which results in postural instability and falling. To achieve stable balance during movement, it is likely that the central nervous system integrates vestibular and leg proprioceptive afferent signals with locomotor commands so that the descending locomotor command to the spinal interneurons is shaped in the context of head position in space and the mechanical state of the limb. However, virtually nothing is known about the interaction between limb movement and head motion, or if these afferent signals and locomotor commands are integrated within the brainstem. This is surprising since information from the limbs is critical to the maintenance of balance, and the limbs serve as the actuators for responding to postural alterations. Central reticular pathways are uniquely positioned to serve as integrators of limb, locomotor, and labyrinthine signals, and then to distribute that integrated signal to the postural muscles, due to their inherent functional connectivity. The primary goals of this application are to determine the nature of the limb input on the activity of reticulospinal neurons and to determine if limb afferen signals are integrated with vestibular afferent signals and locomotor commands at the level of the reticulospinal neuron. Two specific aims are proposed. In the first specific aim, we will characterize the principle sensory afferents responsible for transmitting limb movement information to pontomedullary reticular formation neurons receiving vestibular input. In the second specific aim, we will establish whether reticulospinal neurons integrate vestibular, feedforward locomotor commands, and limb feedback signals. These experiments are expected to advance understanding regarding the processing of limb, labyrinthine, and locomotor inputs in central reticular pathways and may ultimately lead to novel therapies for patients suffering from disorders of locomotion and balance.